The proposed research is directed at defining and characterizing the determinants of the virulence of Neisseria gonorrhoeae and how they interact with the tissues and fluids of the host. The cell envelopes of gonococci will be isolated and fractionated and the components will be characterized chemically, immunologically, and for attachment to mammalian cells and antiphagocytic properties. The envelope components, virulent gonococci, and gonococcal pili will be tested for their potential to injure mammalian cells and elicit release of inflamatory stimuli. The research will examine the effect of antibody to virulent gonococci and to gonococcal components on the expression of the virulence determinants of the bacteria. The research will attempt to confirm the putative virulence- enhancing effect of human tissue extract on gonococci during cultivation in vitro. If the effect is confirmed, the nature of both the effect and of the virulence-promoting activity of the extract will be examined. Finally, the proposed research will compare the virulence determinants of isolates of gonococci from diverse clinical sources to identify and, if found, to define strain-specific properties.